Abstract

Protein synthesis is a tightly regulated cellular process that affects growth, reproduction, and survival in response to both intrinsic and extrinsic cues, such as nutrient availability and energy levels. A pronounced, age-related decline of the total protein synthesis rate has been observed in many organisms, including humans. The molecular mechanisms underlying this decline and their role in the aging process remain unclear. A series of recent studies in the nematode, Caenorhabditis elegans, have revealed a novel link between protein synthesis and aging. Remarkably, these research findings, in their totality, converge to indicate that reduction of mRNA translation prolongs life in worms. Signal transduction cascades implicated in aging, such as the insulin/insulin growth factor-1 pathway, interface with mechanisms regulating protein synthesis via a battery of key mRNA translation factors. Are the effects of these pathways on aging mediated, in part, by alterations in protein synthesis? This is an intriguing possibility in light of the latest discoveries. Whether attenuation of protein synthesis promotes longevity across different phyla is an additional important matter. Here, we survey work associating protein synthesis with aging and discuss the basis of life-span extension under conditions that attenuate protein synthesis.

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